Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study.

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.

Aging and heparin-related bleeding.

BACKGROUND: Many studies have suggested that elderly patients are at increased risk of bleeding during heparin therapy. OBJECTIVE: To establish whether the risk of bleeding in the elderly results from concomitant risk factors or is associated with the aging process itself. METHODS: One hundred ninety-nine patients who presented with proximal deep vein thrombosis were treated with a standard intravenous heparin protocol in a double-blind, randomized, prospective study. Bleeding complications were monitored. Activated partial thromboplastin times and heparin levels were assessed 4 to 6 hours after a standard intravenous heparin bolus and infusion. Heparin doses and heparin levels were also assessed after stable therapeutic heparin infusion rates were established. RESULTS: There was an increase in total and major bleeding complications with aging (P < .05) that was not accounted for by standard risk factors for bleeding. Aging was associated with an increase in heparin levels (r = .239, P = .003) and a tendency for an increase in activated partial thromboplastin time (r = .134, P = .07) after standard heparin doses. Aging was also associated with lower heparin dose requirements (r = .267, P = .003) after therapeutic activated partial thromboplastin times were achieved. CONCLUSION: Aging is a risk for heparin-related bleeding that may be explicable by age-related changes in the pharmacologic characteristics of heparin.

Cognitive impairment in the nondemented elderly. Results from the Canadian Study of Health and Aging.

STUDY OBJECTIVE: To describe a population that was categorized as "cognitively impaired not demented" (CIND) and to examine the utility of some of the proposed criteria for describing this degree of cognitive impairment. DESIGN: Population-based prevalence study of dementia in those subjects who were 65 years and older. SETTING: Community and institutional settings in Canada. SUBJECTS: Individuals who underwent a clinical evaluation (N = 2914). INTERVENTION: Initial screening with the Modified Mini-Mental State Examination (3MS) to identify potential cognitive impairment; the 3MS was followed by a detailed clinical examination to confirm the presence of dementia and to determine the probable cause. Clinical examinations were performed on all those subjects who were residing in institutions, those in the community with a 3MS score less than 78, and a sample of those in the community with a 3MS score of 78 or more. Neuropsychological testing was performed as part of the clinical examination when the 3MS score was 50 or more. At the conclusion of the assessment, subjects were categorized as being cognitively normal, CIND, and demented. MEASUREMENTS: Frequency of a diagnosis of CIND; demographical, cognitive, and functional characteristics of cognitively normal and CIND subjects and those with early and late dementia; and proportion of subjects who were CIND and met the proposed criteria. RESULTS: Subjects who were categorized as CIND were common and fell between cognitively normal subjects and those with dementia in terms of age, 3MS score, general intellectual function, and performance of daily activities. Because of the restrictive inclusion and exclusion criteria, the proposed criteria for cognitive impairment described only 30% of our subjects who were CIND. CONCLUSIONS: Subjects who were categorized as CIND appeared to be distinct from and intermediate between subjects with dementia and cognitively normal subjects. Most individuals did not meet the criteria that were evaluated for describing this group. While the various criteria that were evaluated may accurately define a select subset of cognitively impaired individuals, the natural history and prognosis of such groups, currently unknown, may not be generalizable to the larger population of subjects who are CIND. Further work is needed to clearly define this group, and longitudinal studies are required to determine an outcome.

Creutzfeldt-Jakob disease (CJD) after blood product transfusion from a donor with CJD.

We report a second case of an association between an albumin transfusion and Creutzfeldt-Jakob disease. On balance, we believe our case represents a chance and not a causal relation.

Prevalence and types of dementia in the very old: results from the Canadian Study of Health and Aging.

We report on the prevalence of dementia in Canadians age 85 years and older. The purpose of this study was to determine whether the prevalence of dementia continued to increase in the very old, and to define the types of dementia and their relative proportions in this age group. We collected data as part of the Canadian Study of Health and Aging (1990 to 1992), which consisted of a sample of 1,835 subjects from a population of 283,510 Canadians who were 85 years of age and older residing in the community or in institutions. The prevalence of dementia in the 85 years and older group was 28.5%, more than twice that of the 75- to 84-years cohort. The prevalence of dementia of 23% in the 85- to 89-years sample (n = 1,332) increased to 40% in the 90 to 94 years group (n = 371) and, in the 95 years and older sample (n = 104), reached 58%. Overall, Alzheimer's disease (AD; probable or possible) accounted for 75% of all dementias; a vascular etiology alone accounted for 13% of dementias. The proportion of clinically diagnosed AD cases to vascular dementia cases increased significantly after age 65 and was higher in the 85+ group than in a younger cohort (65 to 84 years).

Prevalence and outcomes of vascular cognitive impairment. Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging.

OBJECTIVE: To assess the importance of vascular cognitive impairment and its three subgroups (cognitive impairment, no dementia; vascular dementia; and AD with a vascular component) to the prevalence and burden of cognitive impairment in elderly people. BACKGROUND: Vascular lesions may produce a spectrum of cognitive changes. Omitting elderly patients whose cognitive impairment falls short of dementia (vascular cognitive impairment, no dementia) may give a falsely low indication of the prevalence and burden of disease. To test this proposition, we compared the rates of adverse outcomes for patients with no cognitive impairment, vascular cognitive impairment (and its subgroups), and probable AD. METHODS: The Canadian Study of Health and Aging is a prospective cohort study of 10,253 randomly selected community-dwelling and institution-dwelling respondents aged 65 years or older. In the community, all participants (n = 9,008) were screened for cognitive impairment; those who screened positive and a sample of those who screened negative received a clinical assessment (n = 1,659). All patients living in institutions received a clinical assessment (n = 1,255). Participants were reassessed 5 years after the original survey. RESULTS: Vascular cognitive impairment without dementia was the most prevalent form of vascular cognitive impairment among those aged 65 to 84 years. Rates of institutionalization and mortality for those with vascular cognitive impairment were significantly higher than those of people who had no cognitive impairment, and the mortality rate for patients with vascular cognitive impairment was similar to that of patients with AD. CONCLUSIONS: Failure to consider vascular cognitive impairment without dementia underestimates the prevalence of impairment and the risk for adverse outcomes associated with vascular cognitive impairment.

Progression of impairment in patients with vascular cognitive impairment without dementia.

Little is known about progression, short of dementia, in vascular cognitive impairment. In the Canadian Study of Health and Aging, 149 participants (79.3 +/- 6.7 years; 61% women) were found to have vascular cognitive impairment, no dementia (CIND). After 5 years, 77 participants (52%) had died and 58 (46%) had developed dementia. Women were at greater risk of dementia (OR 2.1, 1.0 to 4.5). Of 32 participants alive without dementia, cognition had deteriorated in seven and improved in four. Half of those with vascular CIND developed dementia within 5 years, suggesting a target for preventive interventions.

Hypophosphatemic osteomalacia complicating von Recklinghausen's neurofibromatosis: increase in spinal density on treatment.

A 62-year-old white male with neurofibromatosis presented with multiple fractures and bone pain. He was found to have hypophosphatemic osteomalacia secondary to a renal tubular phosphate leak and was treated with phosphate, 1,25-dihydroxycholecalciferol and calcium. With treatment, his dual photon vertebral bone density increased markedly over 12 months. Repeat iliac crest bone biopsies showed that improvement in bone histology was predominantly cortical. This suggests that dual photon absorptiometry of the spine may be markedly influenced by changes in cortical bone status.

Potential adverse outcomes of psychotropic and narcotic drug use in Canadian seniors.

Potential adverse outcomes (falls, impaired cognition, impaired self-care) of psychotropic (benzodiazepines, antidepressants, antipsychotics) and narcotic medication use were examined in a large sample of Canadians 65 years of age and older. We examined rates of reported falls, Digit Symbol Substitution Test (DSST) scores, and mean number of self-care impairments for those consuming psychotropic and/or narcotic drugs as compared to non-users. Use of psychotropic drugs and/or narcotics was associated with an increased prevalence of falls, lower DSST scores, and/or number of self-care difficulties. For example, in subjects who were cognitively normal, the frequency of falls was 60% greater in benzodiazepine users and 120% greater in users of antidepressants as compared to non-users. Adverse outcomes increased with the number of classes of psychotropic or narcotic medications used. These effects were most pronounced in cognitively normal subjects where the prevalence of falls increased from 13.9% in those consuming none of the medication classes to 42.6% for users of two or more classes. In subjects with mild dementia the use of these medications was not associated with any significant differences in the outcomes measured. Regression models showed that benzodiazepine, antidepressant, and narcotic use remained significant explanatory variables for potential adverse outcomes even after simultaneously considering the effects of several other variables. Although further work is necessary, our results suggest that individuals with better cognitive function may be at particular risk for adverse effects with use of these medications.

Marathoners over sixty years of age: results of a survey.

A survey of 32 marathon runners over the age of 60 years was undertaken. The group was predominantly male, well educated, and health conscious. While the injury rate was high, it was comparable to the expected rate in younger runners. Six of the 32 claimed to have an addiction to running.

Aging-related clinical and health services research in Canada.

Research by Canadian geriatricians has grown significantly since the Canadian Society of Geriatric Medicine was founded in 1981. Most research has been clinical or related to health service use. More recently, the Canadian Study of Health and Aging (CSHA) has proved an important focus for population-based research, and research on dementia. An increasing number of Canadian geriatricians have undertaken formal research training, and the CSHA study team and other groups are providing opportunities for multicentre, multidisciplinary, collaborative studies. These developments point to continued growth in research by Canadian geriatricians, most likely research with a clinical and population focus and employing multicenter designs.

Disease, disability, and age in cognitively intact seniors: results from the Canadian Study of Health and Aging.

BACKGROUND: Many diseases have been identified as risk factors for disability in the elderly. This report contrasts disability in the old-old (85 years of age or older, 85+) with younger seniors (65-84 years of age) and examines whether diseases have an equivalent impact on the two groups. METHODS: Subjects were 603 cognitively intact community residents 65 years of age and older from 10 Canadian provinces. The purpose of the analysis was to try to isolate the effects of age and nondementing disease on function. Frequency of disease and functional disabilities was calculated. Logistic regression was used to determine significant explanatory variables for moderate, severe, or total disability and for specific disabilities. RESULTS: Nearly twice as many of the cognitively intact 85+ had functional disabilities compared to those 65-84 years of age. In the 85+, increasing age was the only significant explanatory variable for moderate, severe, or total disability and for problems with walking, showering, shopping, getting to places out of walking distance, and preparing meals. Diseases were also significant explanatory variables for functional disabilities, particularly in the 65-84 age range. An increase in the proportion with functional disability was found with increasing age even in those without the relevant disease risk factors. CONCLUSIONS: Disease prevention would only be partially effective in avoiding disability in the very old because disability occurred even in those without explanatory disease.

Conceptualisation and measurement of frailty in elderly people.

The use of the term 'frailty' has shown tremendous growth in the last 15 years, but this has not been accompanied by a widely accepted definition, let alone agreed-upon measures. In this paper, we review approaches to the definition and measurement of frailty and discuss the relationship between frailty, aging and disability. Two trends are evident in definitions, which often trade off comprehensiveness for precision: frailty can be seen as being synonymous with a single-system problem or as a multisystem problem. The essential feature of frailty is the notion of risk due to instability (itself suggesting a balance of many factors), and has been only poorly measured to date. Future models of frailty should incorporate more precise operationalisation of the probability of frailty and better explain the relationship between disease, disability and frailty.

Nifedipine and mortality risk in the elderly: relevance of drug formulation, dose and duration.

PURPOSE: This study examines the risk of all-cause and cardiac-related mortality associated with calcium channel blockers (CCBs) and other antihypertensives/diuretics compared with beta-blockers among an elderly cohort. We explored variations in mortality risk according to CCB formulation, dose and duration of use. METHODS: Data are from the clinical sample of the Canadian Study of Health and Aging, a population-based prospective study of community and institutional residing persons aged 65+ years. The sample comprised 837 subjects without dementia and reporting use of 1+ antihypertensive/diuretic agents at baseline (1991) and with survival data during follow-up (1996). RESULTS: Risk of all-cause and cardiac-related mortality was significantly higher among nifedipine users (HR=1.85, 95%CI 1.12, 3.05 and HR=2.22, 95%CI 1.02, 4.84, respectively) compared with beta-blocker users. After adjusting for covariates, the hazard ratios (95% confidence interval) for selected drug classes compared with beta-blockers were: nifedipine HR=1.82 (1.09-3.04), diltiazem/verapamil HR=0.96 (0.58-1.60), loop diuretics HR=1.84 (1.21-2.82), ACE inhibitors HR=0.98 (0.54-1.78) and other diuretics/antihypertensives HR=1.10 (0.70-1.72). Among nifedipine users, mortality risk increased with average daily dose and with recent (

Predicting who will develop dementia in a cohort of Canadian seniors.

OBJECTIVES: We examined whether easily attainable variables were useful in predicting who became demented over a five year period and determined the rates of incident dementia for different categories of mild cognitive impairment. METHODS: This was a cohort study of subjects recruited nationally in a population-based survey of Canadians 65 years and older (the Canadian Study of Health and Aging). After standardized clinical assessments, a subset of subjects (n = 1782) was categorized as not demented at time one. Identical study methods allowed a reassessment of the cognitive status of surviving subjects (n = 892) five years later. RESULTS: Three baseline variables (Modified Mini Mental State (3MS) score, subject's age, and an informant's report of the presence of memory problems) were statistically significant predictors of the development of a dementia. An equation incorporating these three variables had a sensitivity of 79% and a specificity of 56% for predicting dementia among survivors at time two. An equation substituting the MMSE for the 3MS showed similar results. The various categories of mild cognitive impairment examined showed significantly different likelihoods for the subsequent development of a dementia. Some categories with a higher dementia risk were characterized by inclusion criteria requiring neuropsychological test scores that were greater than one standard deviation (SD) below the mean of age based normative data. CONCLUSION: In the absence of extensive laboratory, radiologic or neuropsychological tests, simple variables that can be easily determined in the course of a single clinical encounter were useful in predicting subjects with a higher risk of developing dementia. Attempts to use neuropsychological results to predict the development of dementia should look for significant impairments on age-standardized tests.

Recommendations of the Canadian Consensus Conference on Dementia--dissemination, implementation, and evaluation of impact.

BACKGROUND: Subsequent to the development of consensus statements on a clinical topic, it is vital to establish a plan for dissemination, implementation and evaluation of impact. Consensus statements can be used for both guiding continuing medical education (CME) and producing clinical practice guidelines (CPGs). Insufficient attention to dissemination can lead to a failure to change physician behaviour and improve patient outcomes. METHODS: A plan to disseminate the conclusions of the Canadian Consensus Conference on Dementia (CCCD) was developed. This plan was based on a literature review of CME and CPGs. A Medline search was performed on the dissemination and evaluation of the 1989 Canadian Consensus Conference on the Assessment of Dementia (CCCAD) and other published guides for physicians on dementia care. CCCD dissemination that has occurred to date (June, 2000) was reviewed in this paper. RESULTS: Lectures and unsolicited printed material are weak forms of CME. Small-group interactive CME that provides practice opportunities appears to be the most effective way to change physician behaviour. The ability of CPGs to change physician behaviour is uncertain. It appears that inadequate attention has been placed on CPG dissemination and implementation. The CCCAD had a modest impact on clinical practice in Canada. While dissemination of the conclusions of the CCCD has taken place, evaluation of the impact of the CCCD has yet to be done. Local initiatives utilizing the conclusions of the CCCD are on-going. CONCLUSIONS: Further work is needed on how to optimize the impact of consensus statements and CPGs. While dissemination of the CCCD has occurred, it is currently unknown whether it has led to any change in physician practices.

Progression and outcome of patients in a Canadian dementia clinic.

Five hundred and fifty-three patients were referred to a Canadian dementia clinic for standardized evaluation. The majority (83.5%) had a dementia with Alzheimer's disease (AD) accounting for 89% of dementias. Patients with probable AD who were followed for five years had variable rates of progression, increased mortality (37.1%, 2.5 times the expected rate) and a high rate of institutionalization (79%). Simple demographic (age) and social factors (marital status) were strong predictors for institutionalization. It was extremely difficult at presentation to predict the rate of progression. The prevalence of AD in autopsied cases was 62.5%. Clinic patients were younger, had milder dementias, and were more likely to have AD than patients identified in the course of a contemporaneous population-based dementia prevalence study.

The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia.

OBJECTIVE: i) To develop evidence based consensus statements on which to build clinical practice guidelines for primary care physicians towards the recognition, assessment and management of dementing disorders; ii) to disseminate and evaluate the impact of these statements and guidelines built on these statements. OPTIONS: Structured approach to assessment, including recommended laboratory tests, choices for neuroimaging and referral; management of complications (especially behaviour problems and depression) and use of cognitive enhancing agents. POTENTIAL OUTCOMES: Consistent and improved clinical care of persons with dementia; cost containment by more selective use of laboratory investigations, neuroimaging and referrals; appropriate use of cognitive enhancing agents. EVIDENCE: Authors of each background paper were entrusted to: perform a literature search, discover additional relevant material including references cited in retrieved articles; consult with other experts in the field and then synthesize information. Standard rules of evidence were applied. Based upon this evidence, consensus statements were developed by a group of experts, guided by a steering committee of eight individuals from the areas of Neurology, Geriatric Medicine, Psychiatry, Family Medicine, Preventive Health Care and Health Care Systems. VALUES: Recommendations have been developed with particular attention to the context of primary care and are intended to support family physicians in their ongoing assessment and care of patients with dementia. BENEFITS, HARMS AND COSTS: Potential for improved clinical care of individuals with dementia. A dissemination and evaluation strategy will attempt to measure the impact of the recommendations. RECOMMENDATIONS: See text. VALIDATION: Four other sets of consensus statements and/or guidelines have been published recently. These recommendations are generally congruent with our own consensus statements. The consensus statements have been endorsed by relevant bodies in Canada.

Toxicity of lactide in dogs after 2 and 13 weeks of daily oral dosing.

Two-week and 13-week studies were conducted to determine the toxicity of lactide when the compound is administered orally in gelatin capsules to beagle dogs. In the 2-week study, daily doses of 0, 10, 100, 400, 1000 and 2500 mg/kg body weight/day were administered to dogs of both sexes for 14 consecutive days. All dogs survived to the end of the study. Clinical signs consistent with irritation of the alimentary tract occurred in dogs in the 1000 and 2500 mg/kg dose groups. Reductions in body weight gain and in absolute and relative thymus weights were observed in the same two dose groups, and reductions in absolute and relative spleen weights were seen in the 2500 mg/kg dose group. These changes were considered to be secondary to the stress resulting from irritation of the gastrointestinal tract. Gross and microscopic lesions were indicative of irritation, and included dark foci and haemorrhage of the stomach lining, and erosion and ulceration of the stomach and the oesophagus. Also noted in all high-dose dogs was renal tubular regeneration, which may represent repair of previous necrosis of the tubular epithelium. In the 13-week study, no deaths occurred when dogs were given daily oral doses of 0, 4, 20 or 100 mg/kg body weight/day. No clinical signs of toxicity were observed, and the compound had no effect on body weights, food consumption, or any of the clinical chemistry, haematology or urinalysis parameters assessed. Gross and microscopic findings considered to be potentially related to lactide administration were minimal, and included a stomach focus in one dog of each sex in the 100 mg/kg group. The stomach focus in the 100 mg/kg female dog was manifested microscopically as a stomach ulcer. Based on these results, the primary toxic effect of lactide was considered to be irritation of the gastrointestinal tract, and the no-observed-adverse-effect level (NOAEL) after subchronic oral dosing in dogs was considered to be 100 mg/kg/day.

Correlates of self-rated health in persons aged 85 and over: results from the Canadian Study of Health and Aging.

This report describes self-rated health in 1,239 non-institutionalized Canadians aged 85 years and over who participated in the Canadian Study of Health and Aging. Most (76.8%) rated their health positively (i.e., very or pretty good). Stepwise multiple regression was used to determine the variables that were significantly correlated with self-rated health. A modestly successful model for predicting self-rated health (R2 = 0.27) was developed. Better understanding of the determinants of healthy aging hopefully will lead to effective interventions to improve the quality of life of the very old.